Proteopedia

2xc5: Difference between revisions

← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='2xc5' size='340' side='right'caption='[[2xc5]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='2xc5' size='340' side='right'caption='[[2xc5]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xc5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XC5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xc5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XC5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OYJ:(3R,4R)-1-METHANESULFONYL-PYRROLIDINE-3,4-DICARBOXYLIC+ACID+3-[(4-CHLORO-3-FLUORO-PHENYL)-AMIDE]+4-{[2-FLUORO-4-(2-OXO-2H-PYRIDIN-1-YL)-PHENYL]-AMIDE}'>OYJ</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wu1|1wu1]], [[2j34|2j34]], [[2bq7|2bq7]], [[2w3k|2w3k]], [[2vwo|2vwo]], [[1xka|1xka]], [[1nfw|1nfw]], [[2gd4|2gd4]], [[2vvv|2vvv]], [[1msx|1msx]], [[1lpg|1lpg]], [[2vvu|2vvu]], [[1p0s|1p0s]], [[2g00|2g00]], [[1mq6|1mq6]], [[1xkb|1xkb]], [[1iqe|1iqe]], [[1g2m|1g2m]], [[2vh0|2vh0]], [[1nfy|1nfy]], [[2uwl|2uwl]], [[2bok|2bok]], [[1hcg|1hcg]], [[1lpz|1lpz]], [[2w3i|2w3i]], [[1z6e|1z6e]], [[2jkh|2jkh]], [[2uwp|2uwp]], [[1g2l|1g2l]], [[1nfu|1nfu]], [[2bq6|2bq6]], [[1fax|1fax]], [[1iqf|1iqf]], [[1nl8|1nl8]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1lqd|1lqd]], [[2uwo|2uwo]], [[1c5m|1c5m]], [[1ioe|1ioe]], [[1f0s|1f0s]], [[1f0r|1f0r]], [[1mq5|1mq5]], [[2bmg|2bmg]], [[1iqn|1iqn]], [[2bqw|2bqw]], [[1iqm|1iqm]], [[1ezq|1ezq]], [[2vwl|2vwl]], [[2vh6|2vh6]], [[1fjs|1fjs]], [[1lpk|1lpk]], [[2j4i|2j4i]], [[1nfx|1nfx]], [[2vwn|2vwn]], [[2j94|2j94]], [[1iqj|1iqj]], [[2j95|2j95]], [[2cji|2cji]], [[2boh|2boh]], [[2j38|2j38]], [[2w26|2w26]], [[2vvc|2vvc]], [[1iqi|1iqi]], [[2vwm|2vwm]], [[1kye|1kye]], [[1iqk|1iqk]], [[2wyj|2wyj]], [[1v3x|1v3x]], [[2fzz|2fzz]], [[2j2u|2j2u]], [[1ksn|1ksn]], [[1iql|1iql]], [[2wyg|2wyg]], [[2xbx|2xbx]], [[2xby|2xby]], [[2xbv|2xbv]], [[2xc0|2xc0]], [[2xc4|2xc4]], [[2xbw|2xbw]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OYJ:(3R,4R)-1-METHANESULFONYL-PYRROLIDINE-3,4-DICARBOXYLIC+ACID+3-[(4-CHLORO-3-FLUORO-PHENYL)-AMIDE]+4-{[2-FLUORO-4-(2-OXO-2H-PYRIDIN-1-YL)-PHENYL]-AMIDE}'>OYJ</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xc5 OCA], [https://pdbe.org/2xc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xc5 RCSB], [https://www.ebi.ac.uk/pdbsum/2xc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xc5 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xc5 OCA], [https://pdbe.org/2xc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xc5 RCSB], [https://www.ebi.ac.uk/pdbsum/2xc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xc5 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>  
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.  
[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 23: Line 22:
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2xc5 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2xc5 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized.
Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-[[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide] as a clinical candidate.,Anselm L, Banner DW, Benz J, Zbinden KG, Himber J, Hilpert H, Huber W, Kuhn B, Mary JL, Otteneder MB, Panday N, Ricklin F, Stahl M, Thomi S, Haap W Bioorg Med Chem Lett. 2010 Sep 1;20(17):5313-9. Epub 2010 Jul 1. PMID:20650636<ref>PMID:20650636</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xc5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Line 39: Line 29:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Coagulation factor Xa]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Anselm, L]]
[[Category: Anselm L]]
[[Category: Banner, D W]]
[[Category: Banner DW]]
[[Category: Benz, J]]
[[Category: Benz J]]
[[Category: Haap, W]]
[[Category: Haap W]]
[[Category: Schlatter, D]]
[[Category: Schlatter D]]
[[Category: Blood clotting]]
[[Category: Coagulation]]
[[Category: Coagulation factor]]
[[Category: Hydrolase]]
[[Category: Hydroxylation]]
[[Category: Serine protease]]
[[Category: Zymogen]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/2xc5"